Hithertofore, various known antibiotics and antibacterial or antifungal chemical compounds have been used as the agents for controlling or treating therapeutically bacterial or fungal infections. However, some of the known antibiotics and antibacterial chemical compounds can often give side-effects in the patients treated during the therapeutic treatment of bacterial infections due to occurrence of mutation of the microbial strains which are resistant to the antibiotics and/or the antibacterial chemical compounds as administered. In these circumstances, a lasting demand for a new antibacterial or antifungal agent exists. Besides, it is known that such patients having lower immune function than their normal level of the immune function, for example, the tumor-bearing patients and such patients whose immune response has been reduced to an abnormally reduced level by preliminary administration of an immunosuppressive agent before surgical operations for the purpose of facillitating the transplantation of internal organs, are highly susceptible to the opportunistic infection by bacteria and fungi, so that a demand for such a new immunopotentiating agent effective to control and/or treat therapeutically the bacterial and fungal infections is also seen. We, the present inventors, recently have provided such a series of new agents for therapeutic control and treatment of bacterial and fungal infections, which comprise chitin or chitosan as the active ingredients exhibiting the immunopotentiating activities to meet the above-mentioned demands (Japanese patent application first publication "Kokai" Sho No. 59-27827, laid open on 14th February, 1984). Chitin and chitosan are readily available as they occur in large quantities in nature, for instance, in the cell walls of microorganisms and in the outer shells of insects, and Crustacea such as crabs and lobsters.
On the other hand, several agents for therapeutic treatment of malignant tumors which comprise as the active ingredient a polysaccharide or polysaccharides isolated from the cells of microorganisms or from the metabolic products of microorganisms have been proposed in recent years. For example, lentinan, namely such a polysaccharide isolated from the fruit body of a mushroom called "shiitake" (Cortinellus shiitake) (see Japanese patent publication Nos. 37002/72 and 484/74), an antitumor polysaccharide-protein complex as isolated from a mushroom called "kawaratake" in Japan (Coriolus versicolor) (see Japanese patent publication Nos. 23271/80 and 40159/82, U.S. Pat. Nos. 4,271,151, 4,289,688, U.K. Pat. No. 1,565,090 and Canadian Pat. No. 1,084,488), and an antitumor agent comprising the active ingredient such as lipo-polysaccharides isolated from the cell wall of Mycobacterium tuberculosis which is virulent to man(see Japanese patent application first publication "Kokai" Sho No. 57-18619, laid open on 30th January, 1982). We, the present inventors, have also provided an antitumor agent comprising as the active ingredient chitin which is a polysaccharide composed of N-acetylglucosamine residues and exists in large quantities in nature (see Japanese application first publication "Kokai" Sho No. 59-27826, laid open or 14th February, 1984 and the "Microbiology and Immunology" 2, 93, 1984).
The above-mentioned therapeutic agents comprising chitin or chitosan as the active ingredient have remarkable therapeutic activities for control and treatment of the bacterial and fungal infections and for the treatment of tumors. However, both chitin and chitosan are difficult to be formulated into injectable aqueous solutions for intravenous administration because chitin and chitosan are water-insoluble polymers, and hence they are not yet entirely satisfactory in practice to be used in the therapeutic treatment of bacterial and fungal infections and also in the therapeutic treatment of tumors in clinic.
We have made further researches in an attempt to overcome the above-mentioned disadvantages of the chitin and chitosan when used as the antibacterial and antifungal agents and as the antitumor agent. As a result, we have now found unexpectably that several water-soluble chitin-oligomers (otherwise termed as the N-acetyl-chito-oligosaccharides) which are known as the hydrolysis products of chitin, and several water-soluble chitosan-oligomers (otherwise termed as the chito-oligosaccharides) which are also known as the hydrolysis products of chitosan, possess the immunopotentiating activities to stimulate and enhance the immune response in host animals, and are also able to exhibit the inhibitory effects against the infections of bacteria and fungi, as well as the antitumor activity in the same host animals.
The water-soluble chitin-oligomers of which the immunopotentiating activities have now been discovered by us are represented by the following general formula (Ia) ##STR1## wherein n is an integer of from zero to 5; n is zero for di-N-acetyl-chitobiose, n is 1 for tri-N-acetyl-chitotriose, n is 2 for tetra-N-acetyl-chitotetraose, n is 3for penta-N-acetyl-chitopentaose, n is 4 for hexa-N-acetyl-chitohexaose and n 5 for hepta-N-acetyl-chitoheptaose.
The water-soluble chitosan-oligomers of which the imunopotentiating activities have now been discovered by us are represented by the following general formula (Ib) ##STR2## wherein n is an integer of from zero to 5; n is zero for chitobiose, n is 1 is for chitotriose, n is 2 for chitotetraose, n is 3 for chitopentaosne, n is 4 for chitohexaose and n is 5 for chitoheptaose.
Based on our above findings, we have accomplished this invention.
Production and some properties of the chitin-oligomers are described in the "Journal of Chemical Society (C)", 1970, pages 1654-1655, and production and some properties of the chitosan-oligomers are described in the "Journal of American Chemical Society", 79, 5046-5049, 1957, for example.